Shared 6mer Peptides of Human and Omicron (21K and 21L) at SARS-CoV-2 Mutation Sites

Abstract

We investigated the short sequences involving Omicron 21K and Omicron 21L variants to reveal any possible molecular mimicry-associated autoimmunity risks and changes in those. We first identified common 6mers of the viral and human protein sequences present for both the mutant (Omicron) and nonmutant (SARS-CoV-2) versions of the same viral sequence and then predicted the binding affinities of those sequences to the HLA supertype representatives. We evaluated change in the potential autoimmunity risk, through comparative assessment of the nonmutant and mutant viral sequences and their similar human peptides with common 6mers and affinities to the same HLA allele. This change is the lost and the new, or de novo, autoimmunity risk, associated with the mutations in the Omicron 21K and Omicron 21L variants. Accordingly, e.g., the affinity of virus-similar sequences of the Ig heavy chain junction regions shifted from the HLA-B*15:01 to the HLA-A*01:01 allele at the mutant sequences. Additionally, peptides of different human proteins sharing 6mers with SARS-CoV-2 proteins at the mutation sites of interest and with affinities to the HLA-B*07:02 allele, such as the respective SARS-CoV-2 sequences, were lost. Among all, any possible molecular mimicry-associated novel risk appeared to be prominent in HLA-A*24:02 and HLA-B*27:05 serotypes upon infection with Omicron 21L. Associated disease, pathway, and tissue expression data supported possible new risks for the HLA-B*27:05 and HLA-A*01:01 serotypes, while the risks for the HLA-B*07:02 serotypes could have been lost or diminished, and those for the HLA-A*03:01 serotypes could have been retained, for the individuals infected with Omicron variants under study. These are likely to affect the complications related to cross-reactions influencing the relevant HLA serotypes upon infection with Omicron 21K and Omicron 21L.

Molecular mimicry and autoimmunity in the time of COVID-19

“…Based on previous studies, they might induce immunogenic activity [ 30 ]. These results are similar to those from Adiguzel et al [ 138 ], who found, by bioinformatic analysis, that mimicry between SARS-CoV-2 NSP6 with the CRB1 isoform I precursor could be associated with autoimmunity via the interaction with HLA*A02:01 and HLA*A24:02.…”

“…Interestingly, when examining the Omicron variants (i.e., 21 K and 21 L), the molecular mimicry-associated risk appeared to be associated with HLA-A*24:02 and HLA-B*27:05 upon infection with Omicron 21 L. In addition, other Omicron peptides were possible binders to the HLA-B*27:05 and HLA-A*01:01 haplotypes, whereas the binding to HLA-B*07:02 could have been lost or diminished [ 138 ]. It is important to note that the authors of such study used bioinformatic methods to analyze the SARS-CoV-2 proteome and predict the potential binding of viral peptides to MCH molecules.…”

Unveiling the intricacies of COVID‐19: Autoimmunity, multi‐organ manifestations and the role of autoantibodies

“…110 Their findings delineate that, compared to ancestral strains, the Omicron 21K and Omicron 21L variants exhibit altered peptide similarities with human peptides that may provoke distinct autoimmune responses. 110 These novel risks associated with molecular mimicry in the context of Omicron infection are particularly pronounced within the HLA-B27:05 and HLA-A01:01 serotypes. The delineation of particular HLA alleles that confer susceptibility to such autoimmune sequelae upon infection with SARS-CoV-2 variants underscores a genetic predilection that may be pivotal for individualized treatment modalities.…”

“…evaluated the binding affinity between these homologous peptides and human HLA alleles 110 . Their findings delineate that, compared to ancestral strains, the Omicron 21K and Omicron 21L variants exhibit altered peptide similarities with human peptides that may provoke distinct autoimmune responses 110 . These novel risks associated with molecular mimicry in the context of Omicron infection are particularly pronounced within the HLA‐B27:05 and HLA‐A01:01 serotypes.…”

“…Furthermore, Adiguzel et al. evaluated the binding affinity between these homologous peptides and human HLA alleles 110 . Their findings delineate that, compared to ancestral strains, the Omicron 21K and Omicron 21L variants exhibit altered peptide similarities with human peptides that may provoke distinct autoimmune responses 110 .…”